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D Gazit

Publications and source records attributed to D Gazit.

At least 37 records · Page 2Linked to original sources
PubMed1995

Age-related bone loss. A hypothesis and initial assessment in mice.

The osteopenia associated with advanced age appears to be a universal phenomenon in humans and animals, but the mechanisms by which it occurs are understood incompletely. However, the explanation must lie in an absolute or relative diminution in the level of osteoblastic bone-forming activity when compared with osteoclastic bone-resorbing activity. The authors postulated that with old age there would be a reduction in the number or function or both of osteoblastic stem cells that could account for part of the diminution in bone formation. They further postulated that there would be either no change or an increase in osteoclastic potential and bone resorption. To test these concepts, bone marrow cells were isolated from 4- to 6-month-old or 24-month-old mice and cultured in vitro under a variety of circumstances that permitted an assessment of the stromal osteogenic cells and marrow hemopoietic progenitor cells belonging to the monocyte and osteoclast series. These data show a marked reduction in the number and in vitro activity of stromal osteogenic cells from old animals. There is an increase in old mice in the number of marrow cells capable of forming osteoclasts in coculture and responsive to the growth factors believed operational in the monocyte and osteoclast series. The authors now are exploring the hypothesis that an age-related diminution in transforming growth factor-beta levels is responsible for these changes in progenitor cell levels in marrow and their functional status as expressed in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1994

Oral melanocytic lesions: differences in expression of HMB-45 and S-100 antigens in round and spindle cells of malignant and benign lesions.

Immunohistochemistry and melanin bleaching were used to assess the expression of antigens identified by anti-S-100 and anti-HMB-45 antibodies on melanomas and intramucosal and blue nevi from the oral mucosa of 18 patients. Both antibodies reacted with cells in all three types of lesions, but there were differences in the expression of these antigens between the round and spindle cells within the lesions. In melanomas composed of round cells, the intensity and distribution of staining with HMB-45 was greater than with S-100. The opposite was true in melanomas composed of spindle-shaped cells, and one spindle-cell melanoma was HMB-45-negative. The round cells of intramucosal nevi expressed S-100 more intensely and more frequently than HMB-45. The spindle-shaped cells of blue nevi strongly expressed both S-100 and HMB-45. Whereas intradermal nevi from the skin do not express HMB-45, intramucosal nevi consistently express this antigen in the lesion and overlying mucosa. Oral melanomas composed of round and spindle-shaped cells show differences in their expression of S-100 and HMB-45 antigens, making the use of both antibodies complementary in the diagnosis of undifferentiated tumors.

Antibodies, Monoclonal↗
PubMed1993

Ontogenesis of ultrastructural features during osteogenic differentiation in diffusion chamber cultures of marrow cells.

Three stages of osteogenic differentiation can be identified in in vivo diffusion chamber cultures (DCC) of unselected marrow cells, namely, proliferation, differentiation, and maturation (mineralization). These stages were characterized correlatively by in situ differential cell counts, alkaline phosphatase activity, and mineral accumulation. In the present study, the ultrastructure of marrow cell DCC was examined after incubation for 3-21 days. Features characteristic of osteoblastic and chondroblastic differentiation were first noted in 12 day DCC. Sites of osteoblastic differentiation showed cell-cell contacts associated with an increased cell density. The osteoblastic cells had long processes and were embedded in matrix with prominent fiber bundles reminiscent of collagen type I. The chondroblastic cells appeared solitary in areas of lesser cell density. By contrast to the long osteoblastic cell processes, they had short plasmalemmal projections and the matrix surrounding them contained single, thin, short fibers reminiscent of collagen type II, as well as proteoglycan granules. Both cell types showed prominent cytoskeletal elements, rough endoplasmic reticulum, and Golgi. One finding, previously unnoted in differentiating osteogenic cells, was mitochondria with condensed cristae that represent an increased rate of energy metabolism. These mitochondria were particularly abundant in the differentiation stage and declined as the cultures matured. These findings, together with previous reports in the epiphyseal growth plate, suggest that mineralization is associated with an optimal level of energy metabolism rather than extreme hypo- or hyperoxia. The set of ultrastructural parameters defined here in the marrow cell DCC may serve as useful markers for cells undergoing osteogenic differentiation.

Animals↗
PubMed1993

Osteoporosis and increased bone fractures in cerebrotendinous xanthomatosis.

Significant osteoporosis determined by skeleton radiography and bone densitometry was found in 15 patients with cerebrotendinous xanthomatosis (CTX) whose mean age was 31 +/- 11 years. In three CTX patients, bone biopsies confirmed osteoporosis. Nine patients also sustained bone fractures following minimal trauma. Serum 25-hydroxyvitamin D ([25-OHD] 14.6 +/- 6.6 ng/mL v [normal] 30.4 +/- 8.0 ng/mL; P < .001) and 24,25-dihydroxyvitamin D ([24,25(OH)2D] 1.2 +/- 0.4 ng/mL v [normal] 2.7 +/- 0.8 ng/mL; P < .001) levels were low. Serum concentrations of 1,25(OH)2D, calcium, inorganic phosphorus, alkaline phosphatase, parathyroid hormone, and calcitonin were normal. Patients showed classic manifestations of CTX, including dementia, pyramidal and cerebellar insufficiency, peripheral neuropathy, cataracts, and tendon xanthomas associated with elevated serum cholestanol concentrations. These results demonstrate that extensive osteoporosis and increased risk of bone fractures are components of this inherited disease.

Adolescent↗
PubMed1993

Modulation of expression and cell surface binding of members of the transforming growth factor-beta superfamily during retinoic acid-induced osteoblastic differentiation of multipotential mesenchymal cells.

We have evaluated the effects of retinoic acid as a differentiating agent on two pluripotential mesenchymal stem cell lines, the mouse cell line C3H-10T1/2 (10T1/2), which has the capacity to differentiate in vitro into myoblasts, adipocytes, chondrocytes, and osteoblasts, and the rat cell line ROB-C26 (C26), which can, in culture, give rise to adipocytes, myoblasts, and osteoblasts. Retinoic acid (10(-6) M) reduces the incidence of myoblast and adipocyte formation and induces or increases alkaline phosphatase expression and responsiveness to PTH, two indicators of the osteoblastic phenotype. Because transforming growth factor-beta (TGF beta) superfamily members, including the different TGF beta isoforms and the bone morphogenetic proteins (BMPs), are thought to play a role in regulating bone and cartilage formation, and because exogenous TGF beta and BMP-2 have already been found to modulate osteoblastic differentiation of C26 and 10T1/2 cells, we evaluated the endogenous expression of these factors in both cell lines cultured in the presence or absence of retinoic acid. Our data show that C26 and 10T1/2 cells constitutively express a broad spectrum of TGF beta superfamily members. However, this pattern of expression is dramatically altered in response to retinoic acid. Specifically, expression of TGF beta 1 and especially TGF beta 2 is strongly increased, whereas TGF beta 3 expression is down-regulated. These changes are accompanied by a striking decline in TGF beta receptor expression levels at the cell surface. Furthermore, BMP-2 and -4 expression are decreased after treatment with retinoic acid, whereas vgr-1/BMP-6 expression is induced in C26 cells, but decreased in 10T1/2 cells. These results clearly show a dynamic changing pattern of TGF beta superfamily expression consequent to the induction of osteogenic differentiation and provide the first indication that TGF beta receptor down-regulation may be an essential part of this differentiation process. These data also establish the C26 and 10T1/2 cell lines as convenient in vitro model systems for exploring the autoregulation of osteogenic differentiation by members of the TGF beta superfamily.

Animals↗
PubMed1992

Histone H4-related osteogenic growth peptide (OGP): a novel circulating stimulator of osteoblastic activity.

It has been established that regenerating marrow induces an osteogenic response in distant skeletal sites and that this activity is mediated by factors released into the circulation by the healing tissue. In the present study we have characterized one of these factors, a 14 amino acid peptide named osteogenic growth peptide (OGP). Synthetic OGP, identical in structure to the native molecule, stimulates the proliferation and alkaline phosphatase activity of osteoblastic cells in vitro and increases bone mass in rats when injected in vivo. Immunoreactive OGP in high abundance is present physiologically in the serum, mainly in the form of an OGP-OGP binding protein complex. A marked increase in serum bound and unbound OGP accompanies the osteogenic phase of post-ablation marrow regeneration and associated systemic osteogenic response. Authentic OGP is identical to the C-terminus of histone H4 and shares a five residue motif with a T-cell receptor beta-chain V-region and the Bacillus subtilis outB locus. Since these latter proteins have not been implicated previously in the control of cell proliferation or differentiation, OGP may belong to a novel, heretofore unrecognized family of regulatory peptides. Perhaps more importantly, OGP appears to represent a new class of molecules involved in the systemic control of osteoblast proliferation and differentiation.

Amino Acid Sequence↗
PubMed1992

Expression of helix-loop-helix regulatory genes during differentiation of mouse osteoblastic cells.

Although much is known about the hormonal regulation of osteoblastic cell differentiation, much less is known about the nuclear regulatory molecules that affect this process. We analyzed the expression of several regulatory molecules of the helix-loop-helix (H-L-H) group in primary mouse calvarial cells and in MC3T3-E1 mouse osteoblastic cells in situations representing different degrees of cellular differentiation. H-L-H class regulators are known to participate directly in directing cell fate and differentiation decisions in other mesodermal lineages. Two of the molecules that we studied, Id and E12, have well-established roles in this process. The other, mTwi, the murine homolog of the Drosophila twist gene, is a newly cloned mammalian H-L-H gene. Levels of E12 RNA remained unchanged during differentiation. On the other hand, in both primary osteoblastic cells and MC3T3-E1 cells, the abundance of Id and mTwi declined with cell maturation; mTwi less dramatically than Id. That Id expression is causally related to differentiation is suggested by the finding that MC3T3-E1 cells transfected with an Id-expression plasmid fail to undergo differentiation. We conclude that helix-loop-helix regulatory genes are expressed in mouse osteoblastic cells, where they are likely to participate in differentiation. The E12 gene product is likely to function as a positive modulating factor. In contrast, Id inhibits differentiation, probably by sequestering other H-L-H gene regulators, including E12, in inactive complexes. The precise role of mTwi is more speculative at this time, but the observed pattern of expression is consistent with a role in early and midmesodermal specification that is terminated as cells differentiate.

3T3 Cells↗
PubMed1992

Assessment of combined 24,25(OH)2D3 and 1 alpha (OH)D3 therapy for bone disease in dialysis patients.

An increasing body of experimental data suggests a role for 24,25(OH)2D3 in bone metabolism. The present study was carried out to assess a possible therapeutic role of this vitamin D metabolite in renal osteodystrophy. Twenty-two chronic dialysis patients, most of whom were previously maintained on 1 alpha (OH)D3 therapy, received additional treatment with 10 micrograms/day 24,25(OH)2D3 and were compared to 19 patients receiving 1 alpha (OH)D3 alone. Analysis of transiliac bone biopsies obtained at study entry and following 10-16 months of treatment revealed that the combined therapy produced a decrease in bone turnover. Specifically, the addition of 24,25(OH)2D3 inhibited an increase in trabecular bone volume (BV/TV) and suppressed osteoclastic parameters. Thus BV/TV increased from 26.2 +/- 8.6 to 32.1 +/- 7.5% (p < 0.01) in the 1 alpha (OH)D3 group, but it remained unchanged in the combined therapy group. In contrast, the eroded surface (ES/BS), the osteoclast surface (Oc.S/BS), and the osteoclast numbers were significantly suppressed in patients receiving both 24,25(OH)2D3 and 1 alpha (OH)D3, as compared with those receiving 1 alpha (OH)D3 alone (p < 0.01, p < 0.01, and p < 0.001, respectively). These improvements were independent of changes in 1 alpha (OH)D3 dosage. The extent of bone aluminium deposits was unrelated to the administration of 24,25(OH)2D3 or to its effect. 24,25(OH)2D3 therapy was not associated with any adverse effects.

24,25-Dihydroxyvitamin D 3↗
PubMed1991

Leukocytoclastic vasculitis (anaphylactoid purpura): a unique occurrence in the oral cavity.

Leukocytoclastic vasculitis, immune complex disorder (type III), is a skin disease with both an acute form characterized by bullae, vesicles and ulcerations, and a chronic form characterized by petechiae, macules and ulcerations. The disease presents certain systemic features including diffuse or focal glomerulonephritis and renal failure. The histopathologic characteristics of leukocytoclastic vasculitis in the skin appear primarily in small blood vessels and consist of an infiltration of inflammatory cells, leukoclasis, swelling of endothelial cells, occlusion of blood vessels, accumulation of fibrin and fibrinoid degeneration, as well as the presence of immune complexes in and around blood vessel walls. Although leukocytoclastic vasculitis is described as several diseases which can spread systemically, including the gastrointestinal tract and the kidneys, the manifestations of the disease in the oral cavity have not yet been reported. The present paper reports unique oral lesions in a 38-yr-old woman, diagnosed as leukocytoclastic vasculitis, without any accompanying skin or systemic lesions.

Adult↗
PubMed1991

Osteomalacia in hereditary hypophosphatemic rickets with hypercalciuria: a correlative clinical-histomorphometric study.

We characterized the bone disease of transilial biopsy specimens from children with hereditary hypophosphatemic rickets with hypercalciuria (HHRH) and genetically related asymptomatic hypercalciuric subjects. All HHRH patients showed irregular mineralization fronts, markedly elevated osteoid surface and seam width, increased number of osteoid lamellae, and prolonged mineralization lag time. These findings are consistent with a mineralization defect and indicate unambiguously that the bone disease in HHRH is osteomalacia. The only abnormality seen in the asymptomatic hypercalciuric subjects was slightly extended osteoid surface. Parametric and nonparametric statistical analyses performed on a pooled sample of HHRH patients and asymptomatic hypercalciuric subjects revealed a very high inverse correlation and a tight linear relationship between serum phosphorus and osteoid parameters. Serum 1,25-dihydroxyvitamin D, which is low in other forms of hereditary hypophosphatemia and osteomalacia, is elevated in HHRH and correlated positively with osteoid parameters and the mineralization lag time. Serum alkaline phosphatase showed similar relationships. These results as well as the clinical, biochemical, and radiological remission of bone disease consequent to phosphate therapy strongly suggest that in HHRH 1) hypophosphatemia alone is sufficient to cause osteomalacia; and 2) the elevation of 1,25-dihydroxyvitamin D reflects the degree of the primary renal phosphate leak, but is not involved in the pathogenesis of the bone disease.

Absorption↗
PubMed1990

Osteoporosis as the sole presentation of bone marrow mastocytosis.

Three (young) adults with severe generalized osteopenia and vertebral compression fractures were studied. Extensive clinical and laboratory investigations were not contributory. Undecalcified bone biopsies demonstrated multiple mast cell granulomas in the marrow in two patients and numerous mast cells diffusely distributed throughout the bone marrow in the third patient. Mast cells may serve as a pathogenic agent in osteoporosis. Therefore, we conclude that isolated skeletal mastocytosis without clinical evidence of mast cell mediator release should be sought in the evaluation of a patient with unexplained severe bone loss.

Adult↗
PubMed1990

Osteochondral differentiation and the emergence of stage-specific osteogenic cell-surface molecules by bone marrow cells in diffusion chambers.

The osteochondral potential and emergence of osteogenic cell-surface molecules by avian marrow cells was evaluated in in vivo diffusion chamber cultures. The chambers were inoculated with unselected marrow cells from young chick tibiae and implanted intraperitoneally into athymic mice. At the light microscopic level, morphologic evidence of de novo bone and cartilage formation, including specific immunostaining by antibody probes, was observed in 14 out of 16 chambers incubated for 20 days or longer. In order to monitor the osteogenic differentiation of the marrow-derived cells, indirect immunofluorescence was performed with monoclonal antibodies against stage-specific cell surface antigens on cells of the embryonic osteogenic lineage. The binding of these and other specific monoclonal antibodies in the developing tissue indicates that the cell surface and extracellular matrix molecules expressed by descendants of marrow-derived mesenchymal progenitor cells are indistinguishable from their in vivo counterparts found in embryonic skeletal structures. Furthermore, the experiments reported here describe the first molecular identification of osteogenic cells by probes which are selective for stage-specific surface antigens on cells of the osteogenic lineage. Importantly, bone formation by these marrow-derived cells appears to occur through a lineage progression which is similar to that observed for embryonic tibial osteoblasts. In summary, these data support the use of diffusion chambers inoculated with avian marrow to study aspects of osteogenic and chondrogenic differentiation.

Animals↗
PubMed1990

Regenerating marrow induces systemic increase in osteo- and chondrogenesis.

Marrow ablation in long bones induces an increase in osteogenesis in distant skeletal sites. To test the role of marrow regeneration in this phenomenon, rat mandibular condyles were evaluated histomorphometrically during postablation healing of tibial marrow and after inhibition of healing. Ten days after removal of tibial marrow all bone formation parameters in the condylar subchondral bone were markedly elevated, indicating an enhanced osteoblastic activity. The thickness of the cartilaginous zone of calcification was also augmented. These changes were absent when postablation healing was inhibited in the tibia and after massive liver injury. Extensive periosteal injury induced only a slight increase in osteoblast activity. Except for a fall on day 7, the [methyl-3H]thymidine labeling index in the condylar cartilage and oral mucosa remained at control levels 3-18 days after ablation. These findings imply that stimulation of cell proliferation has only a secondary role in the skeletal response to marrow ablation. It is concluded that the systemic increase in osteogenesis occurs preferentially during marrow regeneration and is not a nonspecific skeletal reaction to tissue injury. Apparently, the systemic osteogenic response is mediated by circulating factors produced by the healing marrow; conceptually it is related to other instances where local repair in extraskeletal sites is accompanied by generalized alterations in respective tissues.

Animals↗
PubMed1990

Acromegaly and proximal femoral fracture in an aged person: bone histomorphometry, vitamin D metabolites and parathormone.

Osteoporosis and fractures are rare in acromegaly. An 84-year-old acromegalic woman sustained a fractured neck of femur in a fall. Histomorphometric analysis of an iliac crest biopsy showed marked osteoporosis and augmented resorption parameters. Cortical plates were very thin and bone volume was 8.5%; 12.5% is the reference value for women at this age. The total resorption surfaces were 23.7% compared with the reference value of 8%. We conjecture that postmenopausal and involutional osteoporosis were far advanced before the development of acromegaly, explaining the coexistence of the two conditions. Parathormone (65 pmol/l) and 24,25-dihydroxyvitamin D (1.34 ng/ml) levels were within normal limits, but those of 25-hydroxyvitamin D (5.6 ng/ml) and 1,25-dihydroxyvitamin D (15 pg/ml) were markedly decreased.

Acromegaly↗
PubMed1989

Oral clinicopathologic manifestations in maple syrup urine disease.

Maple syrup urine disease is a rare inborn error of metabolism that manifests mainly by neurologic deterioration, coma, and death in early childhood. Oral manifestations described in this article were mostly gingival enlargement and rampant caries, while histopathologic findings revealed a picture compatible osteomyelitis.

Adolescent↗